This project deals with a cell-type specific surface antigen (LETS protein, SF antigen, here called fibronectin) found in fibroblasts and glia cells. Fibronectin is a high molecular weight glycoprotein and it is present on the surface of normal, but not of malignant fibroblasts or glia cells. The malignant cells do produce fibronectin, but it is not retained on their surface like it is in normal cells. Recent studies show that fibronectin binds to fibrin and collagen and that it promotes agglutination of certain cells. These results suggest that fibronectin may be involved in cell adhesion and perhaps also in growth cotrol. We propose to isolate fibronectin from various sources (normal fibroblasts, spent medium of normal and transformed fibroblasts, plasma) and characterize and compare them biochemically. Antibodies will also be used to study the structure of the fibronectin molecule and its orientation on the cell surface. The capacity of isolated fibronectin to bind to various cells and other materials will be studied. Inhibition of the binding by chemically defined oligosaccharides and polypeptides will be used to work out the specificity of the fibronectin binding site. Purified fibronectin, its fragments and anti-fibronectin antibodies will be used in cell cultures in attempts to define the role of fibronectin in growth control. It is hoped that these studies will add important new information to our knowledge on the membrane changes in malignant cells, growth control as mediated by the normal cell surface and its disturbance in malignant cells.